Background

The CGT pipeline has grown rapidly in the past two decades, following the sequencing of the human genome and the advancement of personalized medicine. The US Food & Drug Administration (FDA) has now approved several cellular, gene, and blood-based therapies, including six chimeric antigen receptor T-cell (CAR-T) therapies. More than 500 CGT products are in active clinical trials. However, despite the promising growth of the sector, product sponsors face continued clinical, regulatory, and market uncertainty.

In recent years, policymakers and agencies have committed to bolstering FDA review capabilities for biologics and CGT, better characterizing evidentiary standards required for novel technologies, and updating payment systems for certain types of CGTs. However, many stakeholder-supported proposals to streamline development for and access to CGTs are still in concept phases.  In part, this is because the individualized nature of many CGT products makes it difficult to establish scientific standards and regulations that apply broadly to a class of technologies. As a result, product sponsors continue to operate with uncertainty regarding development and facing challenges to market access.

Key Considerations

Considering the growing market interest in CGTs, sponsors continue evidence generation planning even though added clarity from regulatory or legislative updates lag behind innovation in the sector. Therefore, it is particularly important for sponsors to identify inflection points during early product development that will influence downstream commercial outcomes. The questions below highlight three such inflection points and describe how a sponsor’s answer to each question may have both regulatory and market access implications.

Who are the intended patients, and how does that shape regulatory and commercial viability?

CGTs often target rare, complex diseases that have a high unmet medical need. As such, a clear understanding of the number and types of patients who may benefit is pivotal to the potential evidence development and access hurdles for the product. Additionally, data collection must balance limited available patients with a demonstration of clinically meaningful benefits in the intended treatment population. Therefore, market sizing, particularly for products targeting extremely rare diseases, is an important early sponsor determination when developing an evidence strategy. Other factors important to this determination include demographic characteristics of the target populations, their socioeconomic circumstances and geographic distribution, and potential access barriers resulting from a limited network of accessible treatment sites. Understanding and planning for these factors early in development will help sponsors reduce future market access and provider uptake barriers.

What FDA regulatory flexibilities can be leveraged to streamline clinical development and filing?

The therapeutic potential of some CGTs provides an opportunity to redefine the current standard of care, filling existing unmet medical needs. This opens doors for manufacturers and FDA to realign on the evidence required for an approval decision. However, there continues to be uncertainty regarding FDA’s approach to risk-benefit assessments and data expectations, given the unique challenges faced by these products and the patients they serve. Currently, sponsors may seek eligibility for relevant expedited development and review designations to gain flexibility and increased engagement with FDA regarding data submissions. Electing one of these routes is often beneficial for timely patient access, especially when the target population may be small and data collection is difficult. However, these methods demand proactive, ongoing evidence generation plans and early engagement with FDA to understand clinical trial design and data requirement flexibilities acceptable to the agency.

How will the product be covered, paid for, and ultimately used by healthcare providers?

The potential value that a CGT may bring to the healthcare system in the long run is still difficult for stakeholders to determine in the absence of long-term real-world evidence. Sponsors will need to determine the value proposition of their therapy for the patient population relative to the patient’s journey from diagnosis to treatment, including mapping out any access barriers patients may face and medical alternatives available on the market. This understanding can help sponsors formulate reimbursement strategies during the clinical phases of development. For example, Avalere has evaluated how CAR-T reimbursement continues to evolve and set precedents for value-based payment strategies; these may become increasingly popular as CGTs gain more presence in the marketplace. Sponsors will also need to consider eligibility for Medicare reimbursement mechanisms such as the New Technology Add-on Payment (NTAP), pass-through payment status, or outlier payments that would apply to their therapy, which can serve to support providers in covering the cost of CGTs.

Even with adequate coverage and reimbursement parameters, healthcare providers and patients may face challenges accessing CGTs. Facilities may require additional investments in staffing, training, or equipment to administer and store these specialty products. Where possible, sponsors are encouraged to support providers and their staff in understanding requirements for handling and administration of these therapies, ultimately helping to mitigate uptake barriers.

Policy Outlook

The policy environment will also influence how sponsors approach these three questions.

For example, collaboration between manufacturers and the FDA has been increasing over recent years, with pilot programs aiming to increase dialogue between sponsors and the agency on data requirements, speed review times, mitigate deficiency letters, and better characterize clinical development in rare, hard-to-treat diseases.

Other proposed policies could have direct impacts on CGTs, such as a pilot program included in the proposed PREVENT Pandemics Act that would implement an advanced manufacturing technologies  designation program. This would provide an expedited FDA pathway for products utilizing a specific platform technology with the potential to streamline development and reduce the regulatory review burden. Other bills include Cures 2.0, with a plethora of potential advancements, including an FDA mandate to report foreseeable challenges to CGT to Congress.

In addition, CGT stakeholders should monitor FDA regulatory guidance (e.g., draft guidance on development of CAR-T therapies) and value assessment reports by groups such as the Institute for Clinical and Economic Review (e.g., report on the need for affordability and access solutions). These materials may provide insight into the scientific and clinical standards required for regulatory approval of products and perspectives on value-based price benchmarks, respectively. Monitoring and assessing these key developments as they occur can help CGT stakeholders navigate the landscape and allocate resources efficiently during commercial launch planning.

Conclusion

CGT development requires an outsized role for early sponsor planning, given the scientific complexity, niche disease targets, and general regulatory uncertainty that these technologies face in the marketplace. Avalere has extensive expertise in evidence generation strategies, market access planning, and policy analysis to support clients in developing comprehensive solutions.

To learn more about how Avalere can support you, connect with us.